Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) [MK-7902-007/E7080-G000-314/LEAP-007] - China Extension Study

NCT04676412 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 7902-007 China ExtensionMK-7902-007E7080-G000-314LEAP-007
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 17

Brief Summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%. The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).

Conditions

Non-small Cell Lung Cancer

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death-ligand 1 (PD-L1, PDL1); programmed cell death-ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

  PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data were from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by BICR per RECIST 1.1 was presented.

  Up to approximately 18 months

• Overall Survival (OS)

  OS was defined as the time from date of randomization to date of death from any cause.

  Up to approximately 18 months

Secondary Outcomes (14)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

  Up to approximately 18 months

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 52 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  Up to approximately 30 months

• Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score

  Baseline and Week 21

• Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score

  Baseline and Week 21

Study Arms (2)

Pembrolizumab + Lenvatinib

EXPERIMENTAL

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Lenvatinib

Pembrolizumab + Placebo

ACTIVE COMPARATOR

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Placebo for lenvatinib

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + Lenvatinib; Pembrolizumab + Placebo

Lenvatinib DRUG

oral capsule

Also known as: MK-7902, E7080, LENVIMA®

Pembrolizumab + Lenvatinib

Placebo for lenvatinib DRUG

oral capsule

Pembrolizumab + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
• Has Stage IV NSCLC (American Joint Committee on Cancer \[AJCC\])
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
• Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score \[TPS\] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory
• Has a life expectancy of ≥3 months
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization
• Male participants must agree to the following during the treatment period and for ≥7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
• Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization
• Has adequate organ function

You may not qualify if:

• Has known untreated central nervous system metastases and/or carcinomatous meningitis
• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
• Has an active autoimmune disease that has required systemic treatment in the past 2 years Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• Has had an allogeneic tissue/solid organ transplant
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
• Has a known history of hepatitis B or known active hepatitis C virus infection
• Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption
• Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability
• Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment
• Has a known history of active tuberculosis (TB)
• Has an active infection requiring systemic therapy
• Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab
• Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (17)

Anhui Provincial Hospital ( Site 0108)

Hefei, Anhui, 230001, China

Location

The First Affiliated Hospital of Anhui Medical University ( Site 0113)

Hefei, Anhui, 230088, China

Location

Peking Union Medical College Hospital ( Site 0105)

Beijing, Beijing Municipality, 100006, China

Location

Beijing Cancer Hospital ( Site 0102)

Beijing, Beijing Municipality, 100036, China

Location

Beijing Chest Hospital Capital Medical University ( Site 0111)

Beijing, Beijing Municipality, 101149, China

Location

Xiangya Hospital of Central South University ( Site 0115)

Changsha, Hunan, 410008, China

Location

Hunan Cancer Hospital ( Site 0104)

Changsha, Hunan, 410013, China

Location

Zhongshan Hospital Fudan University ( Site 0100)

Shanghai, Hunan, 200032, China

Location

Jiangsu Cancer Hospital ( Site 0101)

Nanjing, Jiangsu, 210009, China

Location

The First Hospital of Jilin University ( Site 0110)

Changchun, Jilin, 130021, China

Location

Shanghai Chest Hospital ( Site 0112)

Shanghai, Shanghai Municipality, 200030, China

Location

1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)

XiAn, Shanxi, 710061, China

Location

West China Hospital of Sichuan University ( Site 0117)

Chengdu, Sichuan, 18215516050, China

Location

The First Affiliated Hospital Zhejiang University ( Site 0106)

Hangzhou, Zhejiang, 310003, China

Location

Hangzhou First People's Hospital ( Site 0109)

Hangzhou, Zhejiang, 310006, China

Location

2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)

Hangzhou, Zhejiang, 310009, China

Location

Zhejiang Cancer Hospital ( Site 0116)

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (1)

• Yang JC, Han B, De La Mora Jimenez E, Lee JS, Koralewski P, Karadurmus N, Sugawara S, Livi L, Basappa NS, Quantin X, Dudnik J, Ortiz DM, Mekhail T, Okpara CE, Dutcus C, Zimmer Z, Samkari A, Bhagwati N, Csoszi T. Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial. J Thorac Oncol. 2024 Jun;19(6):941-953. doi: 10.1016/j.jtho.2023.12.023. Epub 2023 Dec 29.

  PMID: 38159809 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: October 23, 2019
• Primary Completion: May 19, 2021
• Study Completion: March 29, 2024
• Last Updated: April 4, 2025
• Results First Posted: November 9, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (17)